Mass spectromety (MS) will be utilized to develop automated methods for quantitative analysis and structure determination applicable to 10 to the minus 6th power to less than 10 to the minus 12th power g samples of biomedical importance. Methods include structure determination of complex molecules utilizing collisional activation (CA) mass spectra to determine fragment structures corresponding to individual spectral peaks. Further studies will be made on MS/MS in which complex mixtures from biological samples are analyzed by component ionization and MS separation followed by identification of the separated ion species through CA or metastable ion decomposition. A tandem double-focusing instrument will be constructed to extend these studies to large biological molecules. An on-line computer will be used for data acquisition and feedback control for this instrument. Laser-enhanced ionization will be used to obtain MS information from biological molecules of low volatility. CA mass spectra and other techniques will be used to extend our knowledge of unimolecular ion decomposition mechanisms.